Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study

Nephrol Dial Transplant. 2018 Mar 1;33(3):523-530. doi: 10.1093/ndt/gfw474.


Background: Protein-energy wasting (PEW) in end-stage renal disease (ESRD) patients is associated with increased morbidity and mortality, but options for treatment are limited. Growth hormone (GH) increases insulin-like growth factor 1 (IGF-1), with improved nutritional parameters, but must be given subcutaneously and does not provide normal GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), maintains normal GH secretion and increases lean body mass in normal subjects; it has not been studied in dialysis patients, an essential step in assessing efficacy and safety prior to clinical trials.

Methods: We performed a randomized crossover double-blind study in assessing the effect of MK-0677 versus placebo on IGF-1 levels, the primary outcome, in hemodialysis patients. In total, 26 subjects enrolled and 22 completed the 3-month crossover study.

Results: The geometric mean IGF-1 was 1.07-fold greater [95% confidence interval (CI) 0.89-1.27; P = 0.718] after placebo. In patients receiving MK-0677, the geometric mean IGF-1 were 1.76-fold greater (95% CI 1.48-2.10; P < 0.001) following MK-0677. When the data were adjusted for preintervention IGF-1 concentration, the ratio of geometric means (MK-0677 relative to placebo) for the pre- versus postintervention change in the IGF-1 was 1.65 (95% CI 1.33-2.04; P < 0.001). These data demonstrate a 65% greater increase (95% CI 33-104%) in IGF-1 in MK-0677-dosed subjects compared with placebo. There were no serious adverse effects attributable to MK-0677.

Conclusions: MK-0677 increased serum IGF-1 levels with minimal adverse effects in hemodialysis subjects. Studies are needed to evaluate whether long-term therapy with MK-0677 improves PEW, lean body mass, physical strength, quality of life and survival in CKD/ESRD patients.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Indoles / administration & dosage*
  • Insulin-Like Growth Factor I / analysis*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / drug therapy
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Prognosis
  • Quality of Life*
  • Receptors, Ghrelin / agonists*
  • Renal Dialysis*
  • Spiro Compounds / administration & dosage*


  • IGF1 protein, human
  • Indoles
  • Receptors, Ghrelin
  • Spiro Compounds
  • Insulin-Like Growth Factor I
  • ibutamoren mesylate